Abstract
The effect of different calcium channel blockers was studied on basal and cocaine-inhibited [ 3H]dopamine uptake in rat striatal synaptosomes. Isradipine (dihydropyridine calcium antagonist) and diltiazem (L-type calaium antagonist) were devoid of effect on [ 3H]dopamine uptake, while flunarizine (T-type calcium antagonist) inhibited [ 3H]dopamine uptake. Flunarizine inhibition was competitive and the inhibitory curve was biphasic with a Hill coefficient of 2.1. The high Hill number suggested a mechanism of positive cooperativity between two sites. Flunarizine inhibition showed a complex interaction with cocaine inhibition. While flunarizine at low concentrations interacts with a distinct site, at higher concentrations it interacts with the same site as cocaine. The relevance of this finding for the potentiation by flunarizine of cocaine-induced dopamine release in vivo is discussed.
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